Table 1.

In vivo studies depicting the main pharmacological proprieties of E. ribes, administered as aqueous/ethanolic extract mainly from berries or other parts of the plant and as pure form.

Animal/Dose	Observation/Outcomes	Ref.
Anticancer
AOM/DSS-induced colon cancer in C57BL/6 male mice/50 mg/d/kg b.w. mixed in diet for 10 days before the CAC challenge, then for 19 or 85 days	↓ Tumor incidence and volume, ↓ IL-6; ↓ STAT3	[88]
DENA/PB-induced liver carcinogenesis in Wistar male rats/50 mg/kg b.w. (p.o.), 14 weeks	↓ Neoplastic nodules	[89]
DMH models in C57 mice, both sexes/100 mg/d/kg b.w. mixed in diet for 30 weeks	↓ Tumor incidence and multiplicity, ↓ PCNA; ↓ Cox-2; ↓ c-Myc; ↓ Survivin	[90]
Female C57BL/6 with H7 or Panc 02 cells -ectopic mouse model/50 mg/kg b.w. i.p. daily, for 2 weeks -orthotopic mouse model/50 mg/kg b.w. i.p. every other day for 1 week	↓ Tumor volume and metastasis	[91]
Male Swiss albino mice solid tumor model with EAC cells/Photodynamic therapy with embelin, 12.5 mg/kg b.w. i.p.	↓ Tumor incidence and volume, ↓ myeloperoxidase, ↓ β-d-glucuronidase and Bcl-2; ↑ Rhodanese and Bax	[92]
In disorders of the CNS
Swiss albino rats and mice/2.5, 5, and 10 mg/kg	Anticonvulsant: ↓ in the duration of HLTE in MES (2.5 and 5 mg/kg, i.p.) Electroshock,100% protection against mortality ↑ Clonic + tonic onsets at all doses	[65]
Swiss albino mice/2.5 and 5 mg/kg	Antidepressant-like effect in TST ↓ Immobility in the FST Exhibited significant activity in mice TST + FST experimental models	[63]
Male Wistar rats/50, 75, 100 mg/kg	Focal cerebral ischemia brain: ↓ infarction and edema (100 mg/kg) Decreased MDA level (75 and 100 mg/kg) ↑ SOD and CAT (100 mg/kg)	[93]
Swiss albino mice/2.5 and 5 mg/kg	Anxiolytic: ↑ Time spent and number of entries in open arm (elevated plus maze) ↓ Duration of immobility in light box (light/dark model) ↑ Rearing assisted rearing and number of squares crossed (open field test) Embelin: anxiolytic effect in dose-dependent manner	[61]
Male Swiss albino mice/10 and 20 mg/kg	Sickness: Embelin prevented anorexia, anhedonia, Ameliorated brain oxidative stress markers Protective effect in LPS-induced sickness behavior	[94]
Adult Wistar rats/10 and 20 mg/kg/day	Huntington′s disease: Loss of b.w. ↓ Oxidative stress ↓ 69–76% brain lesion Protect the neurons from 3-NP toxicity	[95]
Female C57BL/6 mice/25 and 50 mg/kg	Multiple sclerosis (autoimmune encephalomyelitis, CNS inflammation): ↓ Human CD14+ monocyte-derived dendritic cell differentiation ↓ Duction in the EAE clinical score. ↓ Inflammatory Th1 and Th17 cells in EAE.	[96]
Female Sprague–Dawley rats, male C57BL/6 mice/200 nM	Traumatic brain injury: Inhibition of NF-κB expression of XIAP increases in PFT-treated animals. p53 and NF-κB dependent mechanisms delayed neurodegeneration	[97]
Wistar rats’ pups/20 mg/kg	HI-induced neurological injury: Confirm sex differences in behavioral and anatomical outcome XIAP protect the female brain from the early HI injury	[98]
C57BL/6 male, GI female, and Ovx female mice/20 mg/kg	Cerebral ischemia: Inhibitor of XIAP exacerbated stroke-induced injury in females, no effect in males	[99]
Human glioma cell lines T98G, U87MG, and H4. IM-PHFA/0–50 μM	Apoptosis in human glioma cells via NF-κB inhibition: Embelin suppressed proliferation of human glioma cells Apoptosis in human glioma cells by inhibiting NF-κB. ↓ NF-κB activity by reducing nuclear translocation of p65	[76]
Human brain glioma U87 cells/0, 50, and 100 μg/mL	Apoptosis in human glioma cells via the mitochondrial pathway: Time- + dose-dependent apoptosis of brain glioma cells Arrest the cell cycle in the G0/G1 phase Changes in brain glioma cell mitochondrial membrane potential Shifting of Bax and Bcl-2 to cause apoptosis	[100]
Male Wistar rats/25 and 50 mg/kg	Global ischemia/reperfusion-induced brain injury: ↑ Locomotor activity and hanging latency time ↓ Beam walking latency ↓ Lipid peroxidation ↑ Total thiol content and glutathione-S-transferase neuroprotective agent and useful in the treatment of stroke	[60]
Antidiabetics
Albino rats of either sex/100 and 200 mg/kg Wistar rats of either sex/200 mg/kg	Hemodynamic measurement (heart rate, systolic BP), blood glucose, HbA1c, blood GSH, serum marker enzymes (LDH and CK), oxidative stress markers in pancreatic tissue (SOD, CAT, GSH, and LPO), histopathology of pancreatic tissue	[31,41]
Wistar rats of either sex/200 mg/kg	Blood glucose, serum lipid profile (TC, TG and HDL), LPO and protein contents in liver and pancreas	[28]
Wistar rats of either sex/100 mg/kg	HbA1c, blood glucose and GSH, serum marker enzymes (CK, LDH), oxidative stress markers in pancreatic tissue (CAT, SOD, GSH, TBARS), histopathology exam of pancreatic tissue	[101]
Wistar albino rats of either sex/100 mg/kg	Hemodynamic measurement (systolic BP, heart rate), HbA1c, blood glucose	[32]
Male Wistar rats/100 mg/kg	Liver weight, b.w., fasting blood glucose, OGTT, hemodynamic measurement (systolic/diastolic BP, heart rate,); serum adiponectin, insulin, leptin, lipase levels; HOMA-IR values; hepatic glucose-6-phosphatase activity/glycogen content; serum lipid profile (AI, CRI, HDL, LDL, TC, TG, VLDL); oxidative stress markers in liver tissue (CAT, GSH, SOD, TBARS), histopathology exam of liver	[33]

3-NP, 3-nitropropionic acid; AI, atherogenic index; AOM, azoxymethane; ApoB, apolipoprotein B; Bax, Bcl-2 associated x, apoptosis regulator; Bcl-2, B-cell lymphoma 2; BMI, body mass index; BP, blood pressure; b.w., body weight; C57B6, C57 black 6; CAC, colitis-associated cancer; CAT, catalase; CK, creatine kinase; c-Myc, c-myelocytomatosis; CNS, central, nervous system; COX-2, cyclooxygenase-2; CRI, coronary risk index; DENA, Diethyl nitrosamine; DMH, 1,2-dimethylhydrazine; DSS, dextran sodium sulfate; EAC, Ehrlich’s ascites carcinoma; EAE, experimental autoimmune encephalomyelitis; FST, forced Swimming Test; GPx, glutathione peroxidase; GSH, glutathione; HbA1c, glycosylated hemoglobin; HDL, high-density lipoprotein; HFD, high-fat diet; H7, human embryonic stem cell (hESC) line 7; HI, hypoxia-ischemia; HLTE, hind limb tonic extension; HOMA-IR, homeostasis model assessment of insulin resistance; HPLC, high-performance liquid chromatography; IM-PHFA, immortalized primary human fetal astrocytes; IL-6, interleukin-6; i.p., intra peritoneal; ISO, isoproterenol; LDH, lactate dehydrogenase; LDL, low-density lipoprotein; LPO, lipid peroxidation; LPS, lipopolysaccharide; MDA, malondialdehyde; MES, maximal electroshock-induced seizure; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NMR, nuclear magnetic resonance; NPD, normal pellet diet; OGTT, oral glucose tolerance test; PANC02, pancreatic adenocarcinoma epithelial cell line; p-Akt, phosphorylated protein kinase B; PB, phenobarbital; PCNA, proliferating cell nuclear antigen; PFT, pifithrin-alpha; p.o., per os; SOD, superoxide dismutase; STAT3, signal transducer and activator of transcription 3; STZ, streptozotocin; TBARS, thiobarbituric acid-reactive substances; TC, total cholesterol; TG, total triglyceride; TLC, thin layer chromatography; TNF-α, tumor necrosis factor-alpha; TST, tail suspension test; UV, ultraviolet; VLDL, very low-density lipoprotein; XIAP, X-linked inhibitor of apoptosis; ↓, decreasing/reducing; ↑, increasing.